Functional properties of T and B cells isolated by affinity chromatography from rat thoracic duct lymph.
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In many mammals infant behaviour imposes a period during which the young will only take the mother's milk. It is suggested that the immunological components of the milk serve in this period to augment the baby's immune system while he traverses from the antigenic isolation of a fetus to his independent defence. In humans almost all cot deaths occur during this phase. Diverse statistics relating to factors associated with greater risk of cot death are drawn on, suggesting that a number of seemingly unconnected factors can all (including lack of breast-feeding) be interpreted as potential immunity defaults. This interpretation lends support to the idea of an immune mechanism underlying cot death which in some way is an abnormal response resulting from the default and which, with at least one other precipitating mechanism, leads to death.
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A patient with preformed cytotoxic lymphocyte-dependent antibody (L.D.A.) against the specific renal transplant donor rapidly rejected the grafted kidney. The characteristics of rejection were not those of hyperacute rejection due to cytotoxic complement-dependent antibody or of acute rejection is attributed to the cytotoxic activity of L.D.A. The avoidance of transplants based on positive crossmatches by the L.D.A. test or at least the carrying out of the L.D.A. crossmatch is advised.
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Conclusions are difficult to draw. In the six studies of immunotherapy of AML discussed, all the three employing BCG and cells showed a prolongation of survival and the major contributing factor to this prolongation of survival was extension of life after relapse. In the three studies using BCG alone only one shows a beneficial effect, but some more time must be allowed to elapse before this can be concluded with confidence.
Specific suppressor cells have been demonstrated in mice tolerant to the thymus-dependent antigen HGG. Transfer of normal thymocytes, normal spleen cells, or immune spleen cells into these tolerant mice did not restore immunocompetence to HGG. Furthermore, the transfer of tolerant spleen cells into normal recipients abrogated the response of these recipients to subsequent challenge with immunogenic HGG. Spleen cells removed from mice 5, 8, or 11 wk after the induction of tolerance specifically suppressed the response of normal spleen cells in an adoptive cell transfer system. The extent of suppression appears to be dependent upon how long after the induction of tolerance the cells were removed from the tolerant donors and how soon after transfer the recipients were challenged.
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Derivatives of phloretin (25-1,000 mug/ml) among them polyphloretin phosphate (PPP), inhibited in a dose-dependent manner anaphylactic (birch pollen or horse dander) histamine release from human lung tissue passively sensitized with reaginic serum. Pretreatment with PPP of lung tissue sensitized both to birch pollen and horse dander counteracted to a similar extent the release of histamine induced by either allergen administered in sequence. The phloretin derivatives also antagonized the constrictor action of prostaglandin F2alpha on isolated human bronchi at concentrations which did not impair the responses to histamine. The low and high molecular weight derivatives of phloretin were comparably active on a weight basis in both experimental systems.
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PVG rats bearing a transplantable T cell leukemia were treated with large inocula of lymphoid cells from AUG rats sensitized either against the leukemia or against PVG lymphocytes. AUG and PVG bear identical Ag-B antigens but differ at minor loci, including the Pta loci, which code for differentiation antigens expressed only on peripheral T lymphocytes. Treatment with AUG cells immune to either the PVG leukemia or normal PVG cells resulted in prolonged survival of leukemic rats, a profound but ephemeral leukopenia and prolonged disappearance of leukemic cells from lymphoid tissue. All treated animals, however, eventually died with large, discrete deposits of leukemic cells in both hard and soft tissues. Despite the deliberate mismatching of host and donor cells for minor transplanation antigens, no evidence of GVH symptoms was observed in treated rats. This was interpreted as a result of directing the adoptive immune response to antigens of restricted distribution, i.e., on leukocytes and not on somatic cells.
A goat heteroantiserum specific for a rabbit thymus lymphocyte antigen (RTLA) reacted with rabbit basophils resulting in the release of histamine. This activity was equally absorbed out by thymocytes or basophils. Absorption with either of these cell types also resulted in equal loss of thymocytotoxicity. No effect in either system occurred after absorption with either granulocytes or rabbit fibroblasts. These results could not be explained by the presence of immune complexes or aggregated globulin present in the RTLA antiserum. Further, the RTLA anti-serum had no anti-IgE activity, as demonstrated by its lack of reactivity with mast cells that were otherwise capable of releasing histamine normally after challenge with antigen. We have thus shown a basic difference between mast cells and basophils. We conclude that the rabbit basophil may bear a thymic marker.
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Following appropriate immunization of mice with CGG or DNP-CGG spleen cells release antigen upon incubation in vitro. The release can be detected either by 'self-stimulation' of the primed cell population, so that upon adoptive transfer antibodies to CGG and DNP are produced without need for further administration of antigen, or by stimulation of indicator (primed) cells. Boosting mice with antigen in saline following initial immunization with antigen in adjuvant proves the most effective method of loading spleen cells with antigen. A small fraction (10- minus 4- minus 10- minus 5) of the antigen used for boost is retained. The antigen appears to be held on the cell surfaces in the form of antigen-antibody complexes, for it is retained on the cells for up to 13 weeks in the presence of circulating antibody, during which time its capacity to self-stimulate can be inhibited by host serum in vitro. Activated thymus cells take up detectable amounts of antigen-antibody complexes. Complexes obtained by immunization with antigen in adjuvant can be inactivated by trypsinizing spleen cells. Trypsinization of separated T and B cells reveals detectable amounts of complex on the T cells, Complexes detected on T cells in this way are believed to be equivalent to the blocking complexes operative in transplantation and tumour immunity.
E myeloma protein, PS, was reduced in different concentrations of dithiothreitol (DTT) for 1 hr followed by alkylation with 14C-iodoacetamide. The affinity of the reduced-alkylated molecules for target cells was evaluated by their ability 1) to sensitize primate skin in a reversed P-K reaction, 2) to sensitize human basophils in a reversed-type histamine release and 3) to block passive sensitization with reaginic antibody. Antibody-epsilon0 antibody was employed for reversed type reactions to avoid participation of cell-bound normal IgE in the reactions. The sensitizing activity of IgE did not change following reduction in 1 mM DTT, which split inter-heavy-light chain disulfide bond. The activity of IgE significantly diminished after reduction in 2 mM DTT followed by alkylation. This treatment resulted in the cleavage of two intra-epsilon-chain disulfide bonds, which are present between the hinge and the Fd portion of the molecules. The reduced-alkylated protein was capable of sensitizing primate skin and human basophils, however, a much higher concentration of the reduced-alkylated protein than the native protein was required for passive sensitization. The optimal sensitization period for the reversed P-K reaction was 3 hr with the reduced-alkylated protein. The protein had the ability to block passive sensitization with reaginic antibody. The reduced-alkylated protein and the native protein were labeled with 125I, and binding of these proteins with human basophils was examined by autoradiography. The results showed that affinity of the reduced-alkylated protein for basophils was less than that of native protein. Since the disulfide bonds split by 2 mM DTT were not included in the Fc portion of the molecules, the Fc fragment was obtained from the reduced-alkylated protein and was tested for affinity for basophils. It was found that the Fc fragment had higher affinity than the reduced-alkylated protein. Recovery of the affinity by papain digestion strongly suggested that cleavage of disulfide bonds in the Fab portion of the molecules induced conformational changes in the Fc portion which is involved in binding to the target cells. Reduction of IgE with 10 mM DTT followed by alkylation resulted in cleavage of 5 disulfide bonds, which is accompanied by a loss of both sensitizing and blocking activities. The fifth disulfide bond which was cleaved by 10 mM DTT, but not by 2 mM DTT, appears to be an inter-heavy chain disulfide bond in the Fc portion of the epsilon-chains. Neither epsilon1 nor epsilon2 determinants in the Fc portion of epsilon-chains were degraded by this treatment.